We propose to use in vitro irradiations of human lymphocytes as a model system to quantify various cytogenetic detriments resulting from exposure to neutrons of varying energies. Human lymphocytes suspended in culture medium with or without 1M concentrations of the highly efficient OH radical scavenger, dimethyl sulfoxide (DMSO), will be exposed to various energies of neutrons produced by the Van de Graaff accelerator at the Radiological Accelerator Research Facility (RARAF). Our primary aims are to estimate the maximum RBE for chromosome aberrations that arise from DNA damage induced by prompt ionizations vs OH radical attack for monoenergetic neutrons ranging in energy from .22 to 13.9 MeV. In addition, our data will allow us to estimate dose modifying factors for radioprotection against chromosome damage by DMSO for neutrons of each specific energy. In parallel experiments, we will determine the extent to which radiation induced cell cycle delay varies as a function of neutron energy, and how any observed pertubations in cell cycle kinetics are ameliorated in lymphocytes irradiated under conditions of maximum scavenging of OH radicals. We will also derive dose response coefficients for radiation induced micronuclei for neutrons of each energy, and determine whether neutron irradiation results in the induction of DNA lesions that are expressed as sister chromatid exchanges. Lastly, we will conduct studies to determine whether postradiation incubation of neutron lymphocytes in the presence of ARA-C in a potentiation of chromosome damage incurred by prompt ionizations or by OH radical attack. Our overall objectives are to quantify the dose dependency for cytogenetic detriments resulting from "direct" vs "indirect" modes of radiation action, following acute exposures of human cells to monoenergetic neutrons having energies that encompass those of major concern to regulatory agencies responsible for setting human exposure limits. A second objective is to generate experimental data that further define the nature of and mechanisms involved in induction of DNA lesions that lead to chromosome aberrations in human cells following exposure to various qualities of ionizing radiation.